The sentinel node in breast cancer: implications for adjuvant treatment?

Abstract

Despite continuous efforts to define more advanced and less invasive prognostic factors, surgical staging of the axilla remains the single most important prognostic factor in localized breast cancer. Axillary lymph node dissection (ALND) of the lymph nodes at levels I and II, and level III when metastatic involvement is suspected, should provide an answer as to whether metastatic spread to the axilla has occurred. In addition to the presence of axillary involvement per se, the number of axillary nodes involved has a supplementary prognostic impact. In general the axillary lymph node status is defined as follows: 0, 1–3, 4–9 or >10 involved lymph nodes, with crude 10-year survival rates of 65%–75%, 45%–60%, 25%–30% and <20% respectively. Besides prognostic implications, the number of involved lymph nodes also has therapeutic importance. Systemic adjuvant chemotherapy is offered to all lymph node-positive patients and, as recently reported by the Early Breast Cancer Trialists’ Collaborative Group (EBCTCG), produces an absolute improvement of 11% in the 10-year survival of node-positive patients. However, further improvement is clearly warranted and in patients with high-risk primary breast cancer, defined by some authors as having ten or more lymph nodes and by others as having four or more, the value of high-dose chemotherapy with peripheral blood stem cell support is being investigated. Results of the first large randomized trials will be reported in the near future but it is generally not expected that high-dose chemotherapy will have the tremendous impact that was hoped for. In the coming years it is anticipated that the focus of adjuvant treatment will be on further defining the importance of changing the schedule and sequence of relatively standard-dose chemotherapy. In addition, immunotherapy with antibodies against oncogenes, with or without chemotherapy, the development of oncogene/whole cell vaccinations and the importance of interfering with the angiogenesis process will be evaluated. While axillary lymph node invasion is highly indicative for the prognosis, it clearly is not the only important factor since 25%–35% of patients with node-negative disease die of disease within 10 years of diagnosis. High-risk features of the primary tumour such as size, histological grade, nuclear grade, hormone receptor status and vascular and lymphatic invasion, may override the favourable prognosis as determined by the axillary status. In the EBCTCG overview of 69 trials in 36 000 women the proportional reduction in recurrence and mortality due to adjuvant polychemotherapy was independent of nodal status, with a 7% absolute improvement in 10-year survival in the node-negative patients. Does this imply that adjuvant systemic treatment should be given regardless of the axillary nodal status? The International Consensus Panel on the Treatment of Primary Breast Cancer recently published their recommendations on adjuvant treatment, which are as follows: All lymph node-positive patients should be offered some form of chemotherapy and/or tamoxifen. In lymph nodenegative patients it is recommended that patients be categorized into minimal/low risk, intermediate and highrisk groups, where pathological tumour size is considered the most important risk factor. In patients with a tumour size <1 cm, positive oestrogen receptor status, histological and nuclear grade I (the relevance of which is uncertain at this tumour size) and age above 34 years, administration of tamoxifen is optional. If any of these factors are lacking, adjuvant systemic treatment with chemotherapy and/or tamoxifen should be offered. In view of the foregoing information, what will be the role of sentinel node (SN) biopsy with regard to both prognosis and therapy?